Noncoding RNA MaIL1 is an integral component of the TLR4–TRIF pathway
作者： Marina Aznaourova , Harshavardhan Janga , Stephanie Sefried , Andreas Kaufmann , Jens Dorna
关键词:
摘要: RNA has been proposed as an important scaffolding factor in the nucleus, aiding protein complex assembly dense intracellular milieu. Architectural contributions of to cytosolic signaling pathways, however, remain largely unknown. Here, we devised a multidimensional gradient approach, which systematically locates components within cellular networks. Among subset noncoding RNAs (ncRNAs) cosedimenting with ubiquitin-proteasome system, our approach unveiled ncRNA MaIL1 critical structural component Toll-like receptor 4 (TLR4) immune signal transduction pathway. affinity antisense purification-mass spectrometry (RAP-MS) revealed binding optineurin (OPTN), ubiquitin-adapter platforming TBK1 kinase. stabilized OPTN, and consequently, loss blunted OPTN aggregation, TBK1-dependent IRF3 phosphorylation, type I interferon (IFN) gene transcription downstream TLR4. expression was elevated patients active pulmonary infection highly correlated IFN levels bronchoalveolar lavage fluid. Our study uncovers integral TLR4-TRIF pathway predicts further be required for progression networks mammalian cells.
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